The Ca++ available for glomerular filtration consists of the ionized fraction and the amount complexed with anions. Thus about 60% of the Ca++ in plasma is available for glomerular filtration. Normally 99% of filtered Ca++ is reabsorbed by the nephron (Fig. 36.15 ). The proximal tubule reabsorbs about 50% to 60% of the filtered Ca++ . Another 15% is reabsorbed in the loop of Henle (mainly the cortical • Fig. 36.15 Overview of Ca++ transport along the nephron. Percentages refer to amount of filtered Ca++ reabsorbed by each segment. CCD, cortical collecting duct; DT, distal tubule; IMCD, inner medullary collecting duct; PT, proximal tubule; TAL, thick ascending limb.
CHAPTER 36 Potassium, Calcium, and Phosphate Homeostasis portion of the TAL), about 10% to 15% is reabsorbed by the distal tubule, and less than 1% is reabsorbed by the collecting duct. About 1% (200 mg/day) is excreted in urine. This fraction is equal to the net amount absorbed daily by the intestinal tract.
Ca++ reabsorption by the proximal tubule occurs primarily via the paracellular pathway. This passive paracellular reabsorption of Ca++ is driven by the lumen-positive trans-epithelial voltage (Vte) across the second half of the proximal tubule and by a favorable concentration gradient of Ca++ , both of which are established by transcellular sodium and water reabsorption in the first half of the proximal tubule (see
Ca++ reabsorption by the loop of Henle also occurs primarily via the paracellular pathway. Like the proximal tubule, Ca++ and Na+ reabsorption in the TAL parallel each other. These processes are parallel because of the significant component of Ca++ reabsorption that occurs via passive paracellular reabsorption secondary to Na+ reabsorption that generates a lumen-positive Vte. Loop diuretics inhibit Na+ reabsorption by the TAL of the loop of Henle, and in so doing reduce the magnitude of the lumen-positive Vte (see ). This action in turn inhibits reabsorption of Ca++ via the paracellular pathway. Thus loop diuretics are used to increase renal Ca++ excretion in patients with hypercalcemia.
Mutations in the tight junction protein claudin-16 (CLDN16) reduce the permeability of the paracellular pathway to Ca++ and Mg++ and thereby reduce the diffusive reabsorptive movement of Ca++ and Mg++ across tight junctions in the TAL of Henle’s loop. Familial hypomagnesemic hypercalciuria is caused by mutations in claudin-16, which is a component of the tight junctions in TAL cells. This disorder is characterized by enhanced excretion of Ca++ and Mg++ due to a fall in passive reabsorption of these ions across the paracellular pathway in the TAL. Affected individuals have high levels of Ca++ in their urine, which leads to stone formation (nephrolithiasis).